The present invention relates to products and methods useful in the field of high troughput screening and combinatorial experimentation.
Through the years, chemical and pharmaceutical industry have increasingly relied on High Throughput Screening (HTS) of libraries of chemical compounds, biologically active compounds and cells to identify novel materials or compounds with useful properties. HTS describes a method where many discrete compounds are tested in parallel so that large numbers of test compounds are screened for the useful properties. In recent years combinatorial chemistry methodologies have been increasingly applied to the field of materials science, including homogeneous and heterogeneous catalysis, phosphors for luminescent materials, etc. A review has been presented by Jandeleit et al., Angew. Chem. Int. Ed., 1999, 38, 2494-2532. Many references to material design by combinatorial techniques can be found in this review. Combinatorial search for advanced luminescence materials has also been described in Biotech. and Bioeng., (Combinatorial Chemistry), vol. 61, no. 4, pp. 193-201. Combinatorial techniques for developing new materials have also been extensively used in the patent literature: e.g. U.S. Pat. No. 5,985,356, U.S. Pat. No. 6,004,617, U.S. Pat. No. 6,030,917, U.S. Pat. No. 6,043,363, U.S. Pat. No. 6,045,671 and U.S. Pat. No. 6,034,775.
Currently, the most widely established techniques utilise 96-microwell microtiter plates as a substrate for performing the reactions and/or the testing. In this format, 96 independent tests are performed simultaneously on a single 8 cmxc3x9712 cm plastic plate that contains 96 reaction microwells. These microwells typically require assay volumes that range from e.g. 2 to 500 xcexcl. Also microtiter plates with microwells up to 10 or more ml are commercially available.
A problem that arises with such microtiter plates lays in the fact that the construction is truly three dimensional and that the plates occupy, upon storing, quite a large volume. Another problem deals with the microtiter plate handling which requires robots to take the plates out of an input stack, manipulate them for testing, and place them back on a second output stack. Very expensive and complex robots are normally required for this task. True three dimensional movement is necessary and is mostly realised by a rotating arm with extension possibilities and a height control. So rather complex rotational movements must be programmed to come to the required XY-coordinates to handle and analyse the microtiter plates.
The first problem, the required large volume upon storing, can be dealt with by making thinner web materials with a corresponding smaller required stock volume. In WO-A 98/45406 a polymeric substrate is described which is deformed by mechanical pressing so that microvolumes are obtained which can contain the components to be reacted/tested. An additional treatment is required to end up with appropriate hydrophilic/hydrophobic properties. At the end a plate is obtained having thinner substrates and smaller stock volumes after stacking several plates on top of each other.
The second problem, however, remains unsolved, and in most cases the manipulation of thinner plates even becomes much more difficult. Very complex and expensive robots remain required in order to manipulate said discrete web materials.
So there is still a big need to have materials for high throughput screening methodologies which can be handled in a much faster and easier way than conventional plate robots can do.
It is an object of the invention to provide a web material for combinatorial experimentation that is substantially thin and flexible and that has distinct regions that can accommodate fluids and/or solids.
It is a further object of the invention to provide a flexible web material for high speed screening methodologies, that can be incorporated into a simple workflow and apparatus.
It is still a further object of the invention to provide an apparatus for use with such web material, and a method for using such an apparatus for high throughput screening.
Further objects of the invention will become clear from the detailed description hereinafter.
The first object of the present invention is realised by providing a web material for combinatorial experimentation comprising a substrate in web form and multiple microwells, arranged on said substrate in a predetermined pattern and separated from each other by separating zones, each microwell comprising a bottom and an upstanding surface formed by the adjacent separating zones, wherein the composition of said bottoms on the one hand and the composition of said separating zones and upstanding surfaces on the other hand show a different hydrophilicity.
The further object of the invention is realised by providing a simple roll-to-roll device wherein a web material for combinatorial experimentation as defined above is used, the device comprising an unwinding section, a component delivery section, a screening section, and optionally a rewinding section.
The invention further encompasses methods for manufacturing web materials as defined above.